Diabetes, Metabolic Syndrome and Obesity (May 2023)
Renoprotection by Inhibiting Connexin 43 Expression in a Mouse Model of Obesity-Related Renal Injury
Abstract
Xiaomin An,1,2,* Guohua Li,1,* Shu Wang,1 Tianrun Xie,1 Xiaoxiao Ren,1 Yongli Zhao1 1Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China; 2Department of Nephrology, Xi’an Children’s Hospital, Xi’an, 710003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongli Zhao, Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China, Tel +86 0411 84671291, Email [email protected]: Our previous study conducted in an obesity-related renal injury rat model have established a connection between increased connexin 43 (Cx43) expression and renal injury. In this study, we investigated whether inhibiting Cx43 expression could provide renoprotection in a mouse model of obesity-related renal injury.Methods: Five-week-old C57BL/6J mice were fed with a high-fat diet for 12 weeks to establish an obesity-related renal injury model, then they were treated with Cx43 antisense oligodeoxynucleotide (AS) or scrambled oligodeoxynucleotide (SCR) by an implanted osmotic pump for 4 weeks. Finally, the glomerular filtration function, the histological change in the glomeruli, and the markers of podocyte injury (WT-1, Nephrin) and inflammatory infiltration of renal tissue (CD68, F4/80 and VCAM-1) were examined respectively.Results: The results showed that inhibiting Cx43 expression by AS in this mouse model of obesity-related renal injury can effectively improve glomerular filtration function, alleviate glomerular expansion and podocyte injury, and attenuate the inflammatory infiltration of renal tissue.Conclusion: Our results demonstrated that inhibiting Cx43 expression by AS could provide renoprotection for the mouse model of obesity-related renal injury.Keywords: childhood obesity, obesity-related renal injury, connexin 43, antisense oligodeoxynucleotide
